Role of Inflammatory and Proresolving Mediators in Endothelial Dysfunction
Ana M. Briones, Raquel Hernanz, Ana B. García‐Redondo, Cristina Rodrı́guez, Luis Miguel Blanco‐Colio, Almudena Val‐Blasco, María J. Alonso, Mercedes Salaíces
Abstract
Excessive local inflammation is a common mechanism in many cardiovascular diseases (CVDs) such as hypertension, atherosclerosis and aortic aneurysms. In endothelial cells, inflammatory cytokines such as interferons, tumour necrosis factor alpha or interleukins increase oxidative stress and contractile prostanoids and the expression of adhesion molecules that reduce nitric oxide (NO) availability and bind leucocytes, thereby impairing endothelial function. Despite this evidence, anti-inflammatory therapies are not yet indicated for the treatment of most CVD. Resolution of inflammation is mediated by a family of specialized pro-resolving mediators (SPMs) that act on cognate G protein-coupled receptors to limit immune cell infiltration and initiate tissue repair. SPMs, generated from omega-3 and omega-6 polyunsaturated fatty acids, belong to four major families: lipoxins, resolvins, protectins and maresins. SPM receptors are expressed in immune and vascular cells where they regulate important processes such as phagocytosis and polarization, production of cytokines, NO and prostacyclin, and modulation of smooth muscle cell phenotype. Growing evidence in animal models demonstrates that activation of SPM receptors can protect vascular function and structure and provide beneficial effects in various CVD. We will review recent advances in the role of inflammation and SPMs in vascular (dys)function in hypertension, atherosclerosis, and aortic aneurysms.